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The cell proliferation antigen Ki-67 organises heterochromatin

  1. Michal Sobecki
  2. Karim Mrouj
  3. Alain Camasses
  4. Nikolaos Parisis
  5. Emilien Nicolas
  6. David Llères
  7. François Gerbe
  8. Susana Prieto
  9. Liliana Krasinska
  10. Alexandre David
  11. Manuel Eguren
  12. Marie-Christine Birling
  13. Serge Urbach
  14. Sonia Hem
  15. Jérôme Déjardin
  16. Marcos Malumbres
  17. Philippe Jay
  18. Vjekoslav Dulic
  19. Denis LJ Lafontaine
  20. Robert P Feil
  21. Daniel Fisher  Is a corresponding author
  1. Institute for Integrative Biology of the Cell, Université Paris Sud, France
  2. Montpellier Institute of Molecular Genetics, France
  3. Université Libre de Bruxelles, Belgium
  4. University of Montpellier, France
  5. Spanish National Cancer Research Centre, Spain
  6. Mouse Clinical Institute, France
  7. SupAgro, France
Research Article
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Cite this article as: eLife 2016;5:e13722 doi: 10.7554/eLife.13722

Abstract

Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression.

Article and author information

Author details

  1. Michal Sobecki

    Department of Genome Biology, Institute for Integrative Biology of the Cell, Université Paris Sud, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Karim Mrouj

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Alain Camasses

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Nikolaos Parisis

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Emilien Nicolas

    RNA Molecular Biology, Fonds de la Recherche Nationale, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. David Llères

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  7. François Gerbe

    Faculty of Sciences, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Susana Prieto

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Liliana Krasinska

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Alexandre David

    Faculty of Sciences, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Manuel Eguren

    Spanish National Cancer Research Centre, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  12. Marie-Christine Birling

    Mouse Clinical Institute, Illkirch-Graffenstaden, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Serge Urbach

    Faculty of Sciences, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  14. Sonia Hem

    Mass Spectrometry Platform MSPP, SupAgro, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Jérôme Déjardin

    Faculty of Sciences, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  16. Marcos Malumbres

    Spanish National Cancer Research Centre, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  17. Philippe Jay

    Faculty of Sciences, University of Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  18. Vjekoslav Dulic

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  19. Denis LJ Lafontaine

    RNA Molecular Biology, Fonds de la Recherche Nationale, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  20. Robert P Feil

    Montpellier Institute of Molecular Genetics, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  21. Daniel Fisher

    Montpellier Institute of Molecular Genetics, Montpellier, France
    For correspondence
    daniel.fisher@igmm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were performed in accordance with international ethics standards and were subjected to approval by the Animal Experimentation Ethics Committee of Languedoc Roussillon and the Ministry for Higher Education and Research

Reviewing Editor

  1. Fiona M Watt, King's College London, United Kingdom

Publication history

  1. Received: December 10, 2015
  2. Accepted: March 6, 2016
  3. Accepted Manuscript published: March 7, 2016 (version 1)
  4. Version of Record published: April 13, 2016 (version 2)

Copyright

© 2016, Sobecki et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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